1 Which nodes are normally palpable in the healthy individual?

Out of a total of 600, only the submandibular, axillary, or inguinal nodes may at times be felt. Examiner’s skill is, of course, paramount, usually improving with time.

2 What is lymphadenopathy?

The presence of abnormal nodes, because of size, consistency, or number. Adenopathy can occur in various conditions, affecting individuals of any age, and with or without symptoms. It may be happenstance (as incidental detection by the physician or patient during routine exam) or the first sign of malignancy, the presenting manifestation of a complex systemic disorder or a self-limited finding. The differential diagnosis is always challenging.

3 How many adenopathies turn out to be “bad”?

Difficult to say, since data are scarce. In a Dutch study of 2556 patients presenting with unexplained lymph nodal enlargement to a primary care office, 10% were eventually referred to subspecialists, and 3.2% ultimately underwent biopsy. Only 29/2556 (1.1%) had a final diagnosis of malignancy. This low prevalence was confirmed by two separate U.S. studies, suggesting that the much higher neoplastic prevalence of 40–60% reported by many textbooks refers only to the 3% who underwent biopsy, thus grossly overestimating the likelihood of cancer. Hence, in primary care settings, unexplained adenopathy has a neoplastic risk of only 4% in patients 40 years or older and 0.4% in those younger than 40.

4 What is the first approach to adenopathy?

To sort out “serious” from benign. To do so, first separate generalized from localized, since these are distinct conditions with unique differential diagnoses.

5 What is a generalized adenopathy?

One that involves two or more noncontiguous sites (conversely, a localized adenopathy is one that involves only one site). Always make sure that the “localized” ones are not instead part of a generalized process. This may not be necessarily self-evident, since only 17% of all generalized adenopathies are correctly identified by primary care physicians. Hence, whenever you find an abnormal site, always evaluate all others.

6 Where should you look for enlarged nodes?

Important nodes also can be found in the popliteal fossa and paraumbilical region. Deeper ones (hilar, mediastinal, abdominal, and pelvic) are important, too, but inaccessible.

7 Which parts of the exam should be emphasized in cases of generalized adenopathy?

Those that may uncover signs of systemic disease, such as skin rash, mucous membrane lesions, hepatomegaly, splenomegaly, and arthritis.

8 What is the differential diagnosis of a generalizedadenopathy?

One of three processes: (1) a disseminated malignancy, especially hematologic (lymphomas, leukemias, and angioimmunoblastic lymphadenopathy); (2) a collagen vascular disorder (sarcoidosis, rheumatoid arthritis (RA), and systemic lupus erythematosus [SLE]); or (3) an infectious process (mononucleosis, cytomegalovirus [CMV], AIDS, toxoplasmosis, syphilis, tuberculosis, histoplasmosis, coccidioidomycosis, brucellosis, and bubonic plague). Drug reaction can do it, too, and so can intravenous abuse. Some medications (e.g., phenytoin) specifically cause lymphadenopathy; others (e.g., cephalosporins, penicillins, or sulfonamides) do it instead in the context of a serum sickness-like syndrome, with fever, arthralgias, and skin rash (see Table 18-1).

Table 18-1 Medications That May Cause Lymphadenopathy

(Adapted from Ferrer R: Lymphadenopathy. Am Fam Physician 58:1313–1323, 1998.)

9 Should a biopsy be done in patients with generalized lymphadenopathy?

Yes, especially considering the often serious (and systemic) character of the condition. Remember to always biopsy the largest node. If nodes are of similar size, choose in descending order: the supraclavicular, cervical, axillary, epitrochlear, and inguinal stations. The latter is the least helpful, since it often shows only reactive hyperplasia. Yet, do not disregard it. In one retrospective study (with careful patient selection), 53% of inguinal biopsies turned out to be diagnostic. Also, beware that some sites may be more prone to surgical complications than others. Sampling the parotid area, for example, can damage the facial nerve or its branches, while biopsying the posterior cervical triangle may injure the spinal accessory nerve.

10 Which is more common, localized or generalized adenopathy?

Localized. In a primary care setting, 75% of patients will present with localized involvement (head and neck, 55%; supraclavicular, 1%; axillary, 5%; inguinal, 14%).

11 Can the region of involvement narrow the diagnosis?

Yes. As in real estate, location is very important for nodes (as applied, of course, to regional or localized adenopathies). For the generalized form, differential diagnosis is another ballgame). Overall, regional adenopathy reflects localized infection or neoplasm. For instance, cat-scratch disease for cervical or axillary nodes, sexually transmitted diseases for the inguinal ones, and infectious mono for the cervical station. Finally, preauricular nodes (of any size) are usually more significant than similarly sized nodes in other locations.

12 Should one know the regions drained by the various lymphonodal stations?

Yes, since this may unlock the underlying cause. After detecting an enlarged node, always examine the region drained by it (see Table 18-2). Look for infections, skin lesions, or tumors.

Table 18-2 Lymph Node Groups: Location, Lymphatic Drainage and Selected Differential Diagnosis*

STDs = sexually transmitted diseases.

* Modified from Ferrer R: Lymphadenopathy. Am Fam Physician 58:1313–1323, 1998.

13 What are the general characteristics that can help interpret an abnormal node?

The mnemonic is ALL AGES:

14 Why does the patient’s age help?

Because it is the most important predictor of malignancy. Although lymphoproliferative disorders also may affect younger individuals, neoplastic nodes are usually more common in those older than 40 years (Table 18-3). Yet some malignant-looking nodes may actually be benign. Infectious mononucleosis, for example, may often resemble Hodgkin’s disease.

15 What about associated signs and symptoms?

They can be “local” or systemic (Table 18-4). Local findings suggest infection or neoplasm in a specific site (like the swollen nodes and lymphangitic streaks of a skin infection). Conversely, systemic symptoms (such as fever, fatigue, night sweats, and unexplained weight loss) argue in favor of a collagen vascular, lymphoproliferative, or infectious disorder (e.g., tuberculosis [TB]). Still, lack of associated signs or symptoms does not exclude malignancy and thus should not stop a work-up. Finally, remember that the adenopathy of Hodgkin’s disease may become painful after alcohol ingestion.

Table 18-4 Lymphadenopathy—Associated Signs and Symptoms

* Causes of generalized lymphadenopathy.

(Adapted from Ferrer R: Lymphadenopathy. Am Fam Physician 58:1313–1323, 1998.)

16 What about splenomegaly?

It occurs in only 5% of adenopathies, and when it does it argues in favor of sarcoidosis, acute leukemia, chronic lymphocytic leukemia, Hodgkin/non-Hodgkin lymphoma or a mononucleosis-like syndrome. It is instead uncommon in metastatic cancer.

17 What about fever?

It usually suggests infection or lymphoma. Still, the differential diagnosis can be quite wide, since many infectious processes may present with febrile adenopathy (TB, mononucleosis, toxoplasmosis, histoplasmosis, salmonellosis, AIDS, CMV, syphilis, and subacute bacterial endocarditis). Many cancers can do it, too (chronic lymphocytic leukemia [CLL], Waldenström’s, multiple myeloma, and Kaposi’s sarcoma), and so can systemic disorders (sarcoid, SLE, RA, Kawasaki, and Whipple disease).

18 Are there any epidemiologic clues that might narrow the differential diagnosis?

Yes. Occupational exposure, recent travel, or high-risk behavior may all contribute (Table 18-5).

Table 18-5 Epidemiologic Clues to the Diagnosis of Lymphadenopathy

HIV = human immunodeficiency virus.

(Adapted from Ferrer R: Lymphadenopathy. Am Fam Physician 58:1313–1323, 1998.)

19 Which node characteristics can be clinically helpful?

In addition to location, six features may help the diagnosis:

Pearl. Benign nodes tend to be small, soft, nontender, mobile, and discrete (well demarcated). Neoplastic nodes are large, nontender, matted, fixed, and rock-hard. Inflammatory nodes are tender, firm (but not rock-hard), occasionally fluctuant, and often matted and fixed.

20 What is the best way to deal with adenopathy?

21 What is unexplained lymphadenopathy?

id=”p0240″/>One that remains perplexing after initial evaluation. In this case, pursue a specific diagnosis based on the patient’s age, but also the nodes’ duration, characteristics, and location.

22 What is the differential diagnosis of an unexplained lymphadenopathy?

Usually infectious, neoplastic, or autoimmune—which also is the differential diagnosis for fever of unknown origin or an elevated sedimentation rate. A helpful mnemonic is CHICAGO:

23 Which clinical presentations may help identify the cause of lymphadenopathy?

24 How do you palpate cervical nodes?

By using the pads of your fingertips, the hands’ most sensitive parts. Examine both sides of the head and neck simultaneously, by sliding your fingers over the area of attention. Apply steady and gentle pressure. Explore all cervical sites by following the anterior and posterior aspects of the underside of the jaw and neck. Large nodes are often visible, presenting as localized skin bulging. Involvement of only one side of the neck makes these swellings even more visible.

25 What are the important head and neck stations?

There is a fair amount of variability and overlap in pathways of drainage (Fig. 18-1). Overall, you should examine nodes in the following order:

Figure 18-1 Lymph nodes and lymphatic drainage system of the head and neck.

(From Seidel HM, Ball JW, Dains JE, Benedict GW: Mosby’s Guide to Physical Examination, 3rd ed. St. Louis, Mosby, 1995.)

Palpation of other cervical groups also may be indicated in cases of disease affecting specific regions. For example, preauricular and postauricular nodes (just in front or behind the ears) may enlarge because of infections of the external ear canal.

26 And so, what is the overall significance of cervical lymphadenopathy?

It depends on location, but may suggest either infection or malignancy.

Note that one of the processes responsible for isolated posterior cervical and occipital adenopathy is Kikuchi disease (histiocytic necrotizing lymphadenitis). This is a syndrome of unknown etiology first described in 1972 in Japan. The classic patient is a young woman who presents with unilateral painless lymphadenopathy of the posterior cervical region, typically resolving in 3 months.

27 Can cervical nodes remain permanently enlarged after an infection?

Yes. In this case, they are rather small (<1   cm), never tender, and with a rubbery consistency. For example, small palpable nodes in the tonsillar submental and submandibular regions may often occur in otherwise healthy individuals, representing the sequelae of past pharyngitis or dental infections. Conversely, rock-hard nodes should always suggest malignancy, whose location depends on the site drained by the corresponding nodes.

28 What are “shotty” nodes?

They are small nodes that feel like shotgun pellets, or tiny peas. They are typically nontender, firm but not stony-hard, small but equal, mobile, round, and well demarcated. Usually found in the cervical chain of children with viral illnesses (with location reflecting the original site of infection), they may outlast the illness by several weeks and are usually of no clinical consequence. The expression “shotty” was commonly used in 19th-century lay language but is now quite obsolete—except, of course, for medical jargon.

29 What is scrofula?

An old term for cervical tuberculous lymphadenitis: swollen nodes that make the patient’s neck resemble that of a piglet (scrofa, sow in Latin). Scrofula used to be very common in children, since it was spread by unpasteurized milk from infected cows. It was typically treated by the king’s touch, which consisted in having the children’s neck healed by the laying on of his/her majesty’s hands (usually of either England or France). This “cure,” of course, reflected the overall benign nature of the disease rather than the healing power of royalty. Note that chronic mycobacterial (or fungal) infections also can cause supraclavicular adenopathy.

30 What are Delphian nodes?

A cluster of small and midline prelaryngeal nodes (Fig. 18-2). These are typically located on the thyrohyoid membrane—just anterior to the cricothyroid ligament, and just above the thyroid isthmus. Given their pretracheal and superficial location, they are easily palpable if enlarged, even though at times they may be confused with the pyramidal lobe of the gland. They drain the thyroid and larynx, and like Delphi in ancient Greece, they have traditionally been considered an oracle—of thyroid disease or laryngeal malignancy (even though objective supportive data are lacking). They also are the first to be exposed during surgery, thus foretelling the nature of the underlying illness. Delphian nodes reflect a range of thyroid involvement, including subacute thyroiditis, Hashimoto’s, and thyroid cancer. If due to laryngeal carcinoma, they give the disease a more ominous connotation.

Figure 18-2 Associated thyroid masses. A, Pyramidal lobe of the thyroid gland, an upward projection of thyroid tissue, usually arising from the isthmus or left lobe. It may follow the course of the thyroglossal duct as far as the hyoid bone. B, Delphian nodes are enlarged lymph nodes in the thyrohyoid membranes, usually involved only in thyroid carcinoma or subacute thyroiditis.

(From DeGowin RL: DeGowin and DeGowin’s Diagnostic Examination, 6th ed. New York, McGraw-Hill, 1994, with permission.)

31 What is the clinical significance of a palpable supraclavicular node?

An ominous one. A localized node in either the right or left supraclavicular fossa carries a 90% risk of malignancy for patients older than 40 and a 25% risk for younger patients.

32 What is Troisier’s node? What is its significance?

Troisier’s node (or sign) is another name for a palpable single left supraclavicular node. Frequently located just behind the clavicular head of the sternocleidomastoid, it suggests metastasis from a deep-seated carcinoma. Sources include not only the thorax (esophagus or ipsilateral breast and lung), but also the abdomen (stomach, liver, gallbladder, pancreas, kidneys, intestine) and pelvis (ovaries, endometrium, testes, and prostate).

33 Who was Troisier?

Charles E. Troisier (1844–1919) was a graduate of the University of Paris and, subsequently, a professor at the same institution. A well-respected pathologist and clinician, he mostly contributed to the understanding of lymphatic spread by cancer, but also rheumatoid nodules, meningitis, venous thrombosis, and hemochromatosis. In fact, bronzed diabetes (or hemochromatosis) is still referred to as Troisier’s syndrome.

34 What is Virchow’s node?

A left-sided Troisier’s node due to gastric carcinoma.

35 Who was Virchow?

Rudolf Ludwig Karl Virchow (1821–1902) was a graduate of the Friedrich-Wilhelm Institute for Army Doctors in Berlin, which he joined after realizing that his voice was not strong enough to support a career as a preacher. Preaching, however, remained one of his lifelong interests. In fact, after multiple rejections by various journal editors, he founded his own journal, which became known as Virchow’s Archiv, earning its pontificating editor the nickname “The Pope.” Virchow’s contributions to medicine were nonetheless staggering: he was the first to describe (and name) leukemia and understand thrombosis (see Virchow’s triad). He also was the first to recognize cerebral and pulmonary embolism (named that too) and the nature of arterial plugs in malignant endocarditis. He discovered amyloid, myelin, and neuroglia and contributed scores of papers to the understanding of cerebral hemorrhage, meningitis, and various congenital anomalies of the nervous system. By contrast, he had little interest in the emerging germ theory of disease and deeply detested evolution, which he tried to ban from school curricula. Although academically autocratic and reactionary, Virchow was politically very liberal—in fact, almost socialistic. He even helped construct some of the barricades during the 1848 Berlin uprising, a feat that cost him his job. Later, he became an outspoken opponent of Bismarck, who went so far as to challenge him to a duel in 1865 (Virchow agreed but on one condition: that the duel be fought with scalpels). In fact, he never missed a chance to strongly castigate the social injustice and poor hygienic conditions of his time, which he considered responsible for the frequent and recurrent epidemics. In a report to the government that became almost a political indictment of the industrial revolution, he asked, “Shall the triumph of human genius lead to nothing more than to make the human race miserable?” Still, he didn’t limit himself to cursing the darkness, but also lit a few candles—such as securing a good sewerage system and water supply for Berlin. His extracurricular interests included anthropology, medical history, and, above all, archeology. He even accompanied his friend Dr. Heinrich Schliemann to Troy in 1859 (writing an account of his famous discoveries) and concocted the idea of x-raying mummies. When he finally died at 81 from complications of a hip fracture sustained while leaping from a moving tram, it was said that Germany had lost in one single man her leading pathologist, sanitarian, anthropologist, and activist.

36 What is the best way to palpate a supraclavicular node?

Have the patient sit up, with head straight forward and arms down (to avoid mistaking a cervical vertebra or neck muscle for a node). Palpate from behind, since this allows optimal adaptation of your hand to the patient’s anatomy. Conversely, palpate from the front in the supine patient, where the lessened gravity may even mobilize the node and thus make it more accessible. End the exam by asking the patient to perform a Valsalva maneuver, or simply to cough. This may “pop” a deeply seated node, thus bringing it within reach of your fingers.

37 What is the best way to search for axillary nodes?

For the left axilla, grasp the patient’s left wrist or elbow with your left hand, and lift the arm up and out laterally. Then use the tip of your right fingers to palpate deep into the axillary fossa and roof. Do this first with the patient’s arm gently relaxed and passively abducted from the chest wall. Then repeat it with the arm passively and gently adducted. Examine the right axilla in a similar fashion, albeit with a reversed hand positioning. This technique allows the patient’s arm to remain completely relaxed, thus minimizing any tension in the surrounding tissues that could otherwise mask enlarged lymph nodes. It also is easy to carry out on the supine patient, very much as it would be if it were linked with the female breast exam (Fig 18-3).

Figure 18-3 Lymph nodes in the axilla.

(From DeGowin RL: DeGowin and DeGowin’s Diagnostic Examination, 6th ed. New York, McGraw-Hill, 1994, with permission.)

An alternative technique allows simultaneous examination of both axillae. To do so, ask the patient to lift both arms away from the chest. Then extend the fingers of both your hands and gently direct them toward the apices of the armpits. If you don’t want to place your fingers in direct contact with the axilla, you can do this through the patient’s gown. Now press your hands toward the patient’s body, and move them slowly down the lateral chest wall. This allows you to explore the axillary regions in their entirety.

38 What is the clinical significance of axillary adenopathy?

Very much the same as that of cervical adenopathy: cancer and infection (with a sprinkle of systemic disorders, such as sarcoidosis). Note that axillary nodes should not be detectable, even though at times small, mobile, soft, and nontender nodes can be felt in normal people. Larger, tender, but still mobile axillary nodes usually reflect small wounds or infections of the arm (such as cat-scratch fever, tularemia, sporotrichosis, or staphylococcal and streptococcal infections, but also intravenous drug abuse). Conversely, harder, fixed, or matted axillary nodes indicate spread from malignancies, usually of pulmonary or breast origin (but lymphomas and melanomas, too).

39 How do you palpate an epitrochlear node?

By using your right hand to shake hands with the patient’s right hand, while at the same time “cupping” the patient’s elbow with the fingertips of your left hand. Palpate just above the elbow, along the inside of the upper arm, which is where the epitrochlear nodes reside. Then reverse hands and repeat the maneuver on the contralateral side.

40 What is the significance of epitrochlear nodes?

It depends on whether they are isolated or in a generalized setting (25% of adenopathies in other regions also will have palpable epitrochlear nodes). Either way, they are rarely benign. In a prospective study of 324 patients, the two most common causes were infectious mono and non-Hodgkin lymphoma/chronic lymphocytic leukemia, but also sarcoid, HIV, and dermatologic/connective tissue disorders. Historically, the condition has instead been associated with secondary syphilis, lepromatous leprosy, leishmaniasis, and rubella. Finally, an enlarged epitrochlear node also may reflect local inflammation of the hand/forearm. Hence, it is quite common in IV drug abusers.

41 What is the significance of inguinal adenopathy?

Questionable, since most adults have some degree of it, especially if walking shoeless outdoors. Normally, there are two groups of inguinal nodes: one clustered along the inguinal ligament and the other along the femoral vessels. If benign, these tend to be small, firm, and mobile. Yet inguinal adenopathy also may reflect infection or cancer. Hence, when confronted with nodes, make sure to examine the abdomen (look especially for hepatomegaly/splenomegaly), testes, rectum, breasts, genitals, lungs, and skin (look for melanoma). Most common infections are cellulitis and venereal diseases (syphilis, chancroid, genital herpes, and lymphogranuloma venereum). Cancers include instead lymphomas, melanomas, and carcinoma of the penis or vulva. Hence, biopsy of inguinal nodes is usually more informative than that of femoral nodes, which often shows only reactive hyperplasia.

42 What is the node of Rosenmüller-Cloquet?

A deep inguinal node just near the femoral canal, which, if pathologically enlarged, may be mistaken for an inguinal hernia. Instead, it is an important “sentinel” for the tumor status of iliac/obturator nodes. First described by the French Jules Cloquet and the German Johann Rosenmüller—an avid speleologist who had a couple of caves named after him.

43 How significant is a femoral lymphadenopathy?

Very little. Whereas inguinal nodes are lateral in the groin, femoral nodes are medial and closer to the genital area. They are much less significant clinically. In fact, their enlargement often reflects a simple dermatophytosis of the foot.

44 What is the significance of popliteal lymphadenopathy?

Uncertain. Little data exist in humans, since these nodes are often too deep to palpate, and, if palpable, questionable in significance. Hence, authors like Sapira suggest to not even bother (“the physical examination must not be stretched beyond its limits”).

45 What is Sister Mary Joseph’s nodule?

A periumbilical node or hard mass of the navel. It is clinically quite valuable since it represents a direct or lymphonodal metastasis from an intrapelvic/intra-abdominal tumor. The finding was first reported by William J. Mayo in 1928, based on observations by his scrub nurse, Sister Mary Joseph of St. Mary’s Hospital, who could predict laparotomy findings by feeling a periumbilical mass while scrubbing the patient’s abdomen. This is not surprising since the umbilicus is highly susceptible to intra-abdominal metastases, thanks to its multiple anatomic relations and generous vascular/embryologic connections. In fact, in 20% of cases, umbilical metastasis is the presenting manifestation. A total of 407 reports have been published. The usual type is an adenocarcinoma, with the stomach being the most common primary site (23%), followed by ovary (16%), large bowel (10–14%), and pancreas (7–11%). Overall, 52% of cancers are gastrointestinal in origin, and 28% gynecologic; 15% are of unknown primary, and 3% originate instead from the thoracic cavity. In 14–33% of cases, umbilical metastasis is the first (and diagnostic) manifestation of a previously occult neoplasm. In 40%, the nodule is instead an early sign of relapse in a patient with known cancer. Overall, a Sister Mary Joseph’s nodule is a bad omen, since survival is less than 1 year (see also Chapter 15, The Abdomen, question 7).

46 Who was Sister Mary Joseph?

Sister Mary Joseph was born Julia Dempsey in Salamanca, New York, in 1856. In 1878, she entered the congregation of Our Lady of Lourdes and was assigned to the St. Mary’s Hospital in Rochester, Minnesota. There she learned nursing, first working under the guidance of Edith Graham (who subsequently became the wife of Dr. C.H. Mayo) and eventually rising to the position of hospital superintendent, a title she kept until her death in 1939. From 1890–1915, she served as the first surgical assistant to Dr. W.J. Mayo, drawing his attention to the sign that eventually carried her name.